Mitochondria dysfunction and defective protein homeostasis contribute to the onset of several neurodegenerative disorders including Friedreich's ataxia, spastic paraplegia, and Parkinson's disorder as well as normal aging. Mitochondrial protein homeostasis is maintained by localized molecular chaperones and quality control proteases. Chaperones are required for mitochondrial protein import and promote the folding of nascent or recently imported proteins while the quality control proteases degrade those proteins that fail to fold correctly. During stress, a protective mitochondrial-to-nuclear signaling pathway termed the mitochondrial unfolded protein response induces nuclear encoded mitochondrial molecular chaperone gene expression (UPRmt). ATFS-1, is unique in that it has dual compartment specific localization signals; an Nterminal mitochondrial targeting sequence and a C-terminal nuclear localization sequence. This proposal will not only show the presence of coordination of gene expression from the nuclear and mitochondrial genomes during organelle stress, but also substantiate the consequences of un-coordinated expression of the nuclear and mitochondrial genomes.